Vascular calcification (VC) is one of the major causes of cardiovascular morbidity and mortality in patients with chronic kidney disease (CKD). VC is a complex process expressing similarity to bone metabolism in onset and progression. VC in CKD is promoted by various factors not limited to hyperphosphatemia, Ca/Pi imbalance, uremic toxins, chronic inflammation, oxidative stress, and activation of multiple signaling pathways in different cell types, including vascular smooth muscle cells (VSMCs), macrophages, and endothelial cells. In the current review, we provide an in-depth analysis of the various kinds of VC, the clinical significance and available therapies, significant contributions from multiple cell types, and the associated cellular and molecular mechanisms for the VC process in the setting of CKD. Thus, we seek to highlight the key factors and cell types driving the pathology of VC in CKD in order to assist in the identification of preventative, diagnostic, and therapeutic strategies for patients burdened with this disease.

Paraoxonase-1 (PON-1) is a hydrolytic enzyme associated with HDL, contributing to its anti-inflammatory, antioxidant, and anti-atherogenic properties. Deficiencies in PON-1 activity result in oxidative stress and detrimental clinical outcomes in the context of chronic kidney disease (CKD). However, it is unclear if a decrease in PON-1 activity is mechanistically linked to adverse cardiovascular events in CKD. We investigated the hypothesis that PON-1 is cardioprotective in a Dahl salt-sensitive model of hypertensive renal disease. Experiments were performed on control Dahl salt-sensitive rats (SSMcwi, hereafter designated SS-WT rats) and mutant PON-1 rats (SS-Pon1em1Mcwi, hereafter designated SS-PON-1 KO rats) generated using CRISPR gene editing technology. Age-matched 10-week-old SS and SS-PON-1 KO male rats were maintained on high-salt diets (8% NaCl) for five weeks to induce hypertensive renal disease. Echocardiography showed that SS-PON-1 KO rats but not SS-WT rats developed compensated left ventricular hypertrophy after only 4 weeks on the high-salt diet. RT-PCR analysis demonstrated a significant increase in the expression of genes linked to cardiac hypertrophy, inflammation, and fibrosis, as well as a significant decrease in genes essential to left ventricular function in SS-PON-1 KO rats compared to SS-WT rats. A histological examination also revealed a significant increase in cardiac fibrosis and immune cell infiltration in SS-PON-1 KO rats, consistent with their cardiac hypertrophy phenotype. Our data suggest that a loss of PON-1 in the salt-sensitive hypertensive model of CKD leads to increased cardiac inflammation and fibrosis as well as a molecular and functional cardiac phenotype consistent with compensated left ventricular hypertrophy.

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Purpose The effect of preoperative endoscopic tattooing (ET) on accurate colorectal cancer localization and resection has been well established. However, its effect on lymph node (LN) retrieval remains unclear. The purpose of this study was to systematically compare LN retrieval between patients with colorectal cancer who underwent preoperative ET and those who did not. Methods A systematic search for relevant studies was conducted using the following databases: PubMed, Embase, and Web of Science. Studies that compared LN retrieval in patients with colorectal cancer with and without preoperative ET were included. Weighted pooled odds ratio (OR) and mean difference (MD) with the corresponding 95% confidence intervals (CIs) for all outcomes using the random-effects model were calculated. Results 10 studies, including 2231 patients with colorectal cancer were included. Six studies reported total LN yield and showed significantly higher LN yield in the tattooed group (MD:2.61; 95% CI:1.01–4.21, P = 0.001). Seven studies reported the number of patients with adequate LN retrieval and showed a significantly higher number of patients with adequate LN retrieval in the tattooed group (OR:1.89, 95% CI:1.08–3.32, P = 0.03). However, subgroup analysis revealed that both outcomes were only statistically significant in patients with rectal cancer, and not in patients with colon cancer. Conclusions Our results suggest that preoperative ET is associated with increased LN retrieval in patients with rectal cancer, but not in colon cancer. Further large-scale randomized control trials are necessary to validate our findings.